NM_001402.6:c.22A>G

Variant names:

• chr6-73520005-T-C
• rs775774223
• NM_001402.6:c.22A>G
• EEF1A1 p.Ile8Val

Variant summary

Our verdict is

Likely benign

-5 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_001402.6(EEF1A1):​c.22A>G​(p.Ile8Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000691 in 1,446,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: EEF1A1 NM_001402.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91
• Publications: 1 publications found

Genes affected

EEF1A1 (HGNC:3189): (eukaryotic translation elongation factor 1 alpha 1) This gene encodes an isoform of the alpha subunit of the elongation factor-1 complex, which is responsible for the enzymatic delivery of aminoacyl tRNAs to the ribosome. This isoform (alpha 1) is expressed in brain, placenta, lung, liver, kidney, and pancreas, and the other isoform (alpha 2) is expressed in brain, heart and skeletal muscle. This isoform is identified as an autoantigen in 66% of patients with Felty syndrome. This gene has been found to have multiple copies on many chromosomes, some of which, if not all, represent different pseudogenes. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.239).
• BS2: High AC in GnomAdExome4 at 10 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001402.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEF1A1	NM_001402.6	MANE Select	c.22A>G	p.Ile8Val	missense	Exon 2 of 8	NP_001393.1	P68104

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EEF1A1	ENST00000309268.11	TSL:1 MANE Select	c.22A>G	p.Ile8Val	missense	Exon 2 of 8	ENSP00000339053.4	P68104
	EEF1A1	ENST00000316292.13	TSL:1	c.22A>G	p.Ile8Val	missense	Exon 1 of 7	ENSP00000339063.7	P68104
	EEF1A1	ENST00000850909.1		c.22A>G	p.Ile8Val	missense	Exon 2 of 9	ENSP00000520989.1	A0ABJ7HDN8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000417 AC: 1 AN: 239992 AF XY: 0.00000765

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000890

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000691 AC: 10 AN: 1446578 Hom.: 0 Cov.: 31 AF XY: 0.00000972 AC XY: 7 AN XY: 720094

African (AFR) AF: 0.00 AC: 0 AN: 33268

American (AMR) AF: 0.00 AC: 0 AN: 44230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26074

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85880

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4542

European-Non Finnish (NFE) AF: 0.00000810 AC: 9 AN: 1111444

Other (OTH) AF: 0.00 AC: 0 AN: 60128

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	26
DANN	Benign	0.95
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.058
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-1.1	T
PhyloP100		7.9
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.24
Sift	Benign	0.098	T
Sift4G	Benign	0.16	T
PromoterAI		0.011	Neutral
Varity_R		0.17
gMVP		0.95
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs775774223;

hg19: chr6-74229728;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline